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Background: The purpose of the study was to examine whether penicillin-susceptible and nonsusceptible strains of Streptococcus pneumoniae exhibited different pharmacodynamic responses to benzylpenicillin. Methods: The postantibiotic effects (PAEs) and the postantibiotic sub-MIC effects (PA SMEs) were investigated by optical density against strains of S. pneumoniae with different susceptibilities to benzylpenicillin. To validate the data, the PAE and PA SME of one susceptible and one resistant strain were also tested with the viable count method. The post-MIC effects (PMEs) were studied in an in vitro kinetic model, simulating human pharmacokinetics with a half-life of 1 h and a time above MIC of approximately 20% of 24 h. Results: There were no differences with respect to the PAEs, PA SMEs and PMEs of benzylpenicillin for the various strains of S. pneumoniae, irrespective of their susceptibility to penicillin. For both some of the susceptible and resistant strains investigated, longer PA SMEs at 0.2 and 0.3 × MIC were noted, indicating that these parameters might be more dependent on the type of strain rather than on the susceptibility status. Conclusion: No differences in the pharmacodynamic response after similar drug exposure were seen for S. pneumoniae strains with different penicillin susceptibility.

The synthesis from penicillin G of a series of potent pseudosymmetric inhibitors 11 a-k of HIV-1 proteinase is described. The 2-pyridyl substituted compounds 11a and 11j showed improved antiviral activity compared to their C2-symmetric counterparts 3 and 4.

The reactive extraction (re-extraction) of penicillin G from reaction mixtures is based on complexation with a carrier and subsequent dissociation of the complex. An established mathematical model for this has been analysed to develop a feasibility domain within which the process may be designed and optimised. Geometric and physical interpretations of this domain are provided.

The mixed metabolism model of Nicolaiet al. (1991) has been used to analyse the sensitivity of fed-batch fermentation for penicillin G with respect to four parameters. The cases of fully endogenous, fully maintenance and mixed metabolisms have been studied. Sensitivities with respect to two parameters,K x andK i, were much larger than for the other two. Differences between the three kinds of metabolism were sharpest forK p. The implications of both observations are discussed.

In this paper, an updated unstructured mathematical model for the penicillin G fed-batch fermentation is proposed, in order to correct some physical and biochemical shortcomings in the model of Heijnen et al. (1979,Biotechnol. Bioeng.,21, 2175–2201) and the model of Bajpai and Reus (1980,J. Chem. Tech. Biotechnol.,30, 332–344). Its main features are the consistency for all values of the variables, and the ability to adequately describe different metabolic conditions of the mould. The model presented here can be considered as the translation of the latest advances in the biochemical knowledge of the penicillin biosynthesis.

Serum concentrations of penicillin were measured in children with rheumatic fever. The adequacy of the values after administration of 1.2 million units of benzathine penicillin G every 2 or 3 weeks was confirmed; the adequacy of a 4-week regimen was questionable. The administration of 0.6 million units every 3 weeks was found to be inadequate to maintain serum levels high enough for the secondary prophylaxis of rheumatic fever.

A rapid enzyme-linked immunosorbent assay (ELISA) for the detection of penicillin G in milk at concentrations of 6 ng/ml (0.01 IU/ml) was used to screen 1651 off-farm milk samples previously reported as containing no detectable levels of antimicrobial substances. Using a single-well per test format and a percent inhibition cut-off for the determination of positive/negative endpoint, 3.1% positives were obtained. Comparison with intra-assay standards lowered the numbers of positives to 0.42%. Analysis of 170 milk samples positive for antimicrobials confirmed 92.4% as containing penicillin G using the prescribed cut-off level and 87.6% when compared to standards. The ELISA, now available commercially in kit form, analyses between 1 and 48 samples in 15 minutes. It will detect 0.01 IU/ml to a level of confidence of 99% and 0.005 IU/ml with between 75 and 95% confidence.

Plasma penicillin levels were studied 2, 3, and 4 weeks after intramuscular benzathine penicillin G (BPG) doses of 1,200,000, 1,800,000, and 2,400,000 U. Proportions of patients with penicillin levels above 25 ng/ml at each week increased with increasing BPG dose. Further studies of higher-dose BPG for rheumatic fever prophylaxis are required.

The susceptibility to penicillin of 6 prevalent pneumococcal types isolated from nasopharynx in 1992 was compared with that of corresponding types from 1980–82. The 6 types or groups, 6, 9, 14, 15, 19 and 23, constituted 78% of consecutive isolates. 19/204 isolates in 1992 were intermediately resistant (MIC 0.12–1.0 mg/1) in comparison with 1/194 from 1980–82 (p < 0.001). Resistant strains (MIC ⩾ 2 mg/1) were not found. Of group 15, no fewer than 10/31 isolates were intermediately resistant, which may support the clonal origin and spread of penicillin-resistant pneumococci. At least 5.0% of nasopharyngeal isolates are now intermediately resistant to penicillin. This figure is substantially higher than the 2% earlier reported in Sweden.

Practical procedures have been developed for synthesis of peptides using lipase as catalyst.

The kinetics of reextraction of penicillin from the LA-2-penicillin complex-n-butylacetate solution by phosphate buffer was investigated experimentally and theoretically. The concentration time functions can be described by a mathematical model in a wide range of pH-values and complex concentrations.

The reextraction of Penicillin G from the Penicillin-LA-2 complex in n-butyl acetate by phosphate buffer was investigated in a bench-scale Karr column. The influence of stroke frequency, pH-value and the throughput of the organic phase were studied. Penicillin V was extracted from fermentation broth and reextracted by phosphate buffer. The extraction is hampered by the proteins precipitated during the extraction. The elimination of this effect is discussed.